This investigation examines the biochemical changes in the connective tissue of the uterine cervix in relation to pregnancy and the onset of labor. Using fixation with Safranin O in glutaraldehyde, progressive increase was seen throughout pregnancy in an amorphous material that dispersed collagen bundles and fibers. There was no significant structural difference in the extracellular matrix either radially or longitudinally. Studies of human cervical biopsies obtained post partum and from hysterectomy specimens confirmed the measurement in rats of increasing hyaluronate content by the end of pregnancy. There was a two fold increase in hyaluronate content per unit and three fold increase in hyaluronate concentration per hydroxyproline concentration where as dermatan sulfate concentration was unchanged. Rat studies demonstrated a high concentration of a specific lysosomal hyaluronidase in the cervix which increased even more in pregnancy in proportion to hyaluronate increase and which then disappeared post partum. Examination of the dermatan sulfate proteoglycan from sheep cervix prepared by neutral isotonic buffer extraction followed by 4 M GuCl2 extraction showed that the presumed proteoglycan subunit in this fibrous tissue is much lighter and slightly smaller than corresponding chondroitin sulfate components of hyaline cartilage.